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A new study provides evidence for what so many people complain about - that after being treated for Lyme disease with several weeks of antibiotics - they feel that they are not cured, but instead still suffer from Lyme disease. Lyme disease is caused by the bacterium Borrelia burgdorferi, which is transmitted to a person during a tick bite. However, many medical professionals deny that a person can still have Lyme disease after antibiotic treatment, and instead call the lingering symptoms post-treatment Lyme disease syndrome (PTLDS). It is thought that between 10 to 20% of persons treated with antibiotics for Lyme disease have symptoms of PTLDS.

Hah! The Tulane University researchers found that yes, the live bacteria (B. burgdorferi spirochetes) can still be there in different organs of the body even after 28 days of antibiotic treatment. They studied late Lyme disease in both treated (with antibiotics) and untreated rhesus macaques - primates in which Lyme disease has effects similar to humans. Other studies have also found that the Lyme disease bacteria can evade treatment (here and here). From Medical Xpress:

Lyme bacteria survive 28-day course of antibiotics months after infection

Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced results of two papers published in the peer-reviewed journals PLOS ONE and American Journal of Pathology, that seem to support claims of lingering symptoms reported by many patients who have already received antibiotic treatment for the disease. Based on a single, extensive study of Lyme disease designed by Tulane University researchers, the study employed multiple methods to evaluate the presence of Borrelia burgdorferi spirochetes, the bacteria that cause Lyme disease, before and after antibiotic treatment in primates.

The data show that living B. burgdorferi spirochetes were found in ticks that fed upon the primates and in multiple organs after treatment with 28 days of oral doxycycline. The results also indicated that the immune response to the bacteria varied widely in both treated and untreated subjects. "It is apparent from these data that B. burgdorferi bacteria, which have had time to adapt to their host, have the ability to escape immune recognition, tolerate the antibiotic doxycycline and invade vital organs such as the brain and heart," said lead author Monica Embers, PhD, assistant professor of microbiology and immunology at Tulane University School of Medicine.

"In this study, we were able to observe the existence of microscopic disease and low numbers of bacteria, which would be difficult to 'see' in humans but could possibly be the cause of the variable and nonspecific symptoms that are characteristic of post-treatment Lyme disease syndrome. Although current antibiotic regimens may cure most patients who are treated early, if the infection is allowed to progress, the 28-day treatment may be insufficient, based on these findings," Embers said.

The findings also demonstrated: All subjects treated with antibiotics were found to have some level of infection 7 - 12 months post treatment. Despite testing negative by antibody tests for Lyme disease, two of 10 subjects were still infected with Lyme bacteria in heart and bladder. Lyme bacteria which persist are still viable.

To better elucidate previous animal studies demonstrating that some B. burgdorferi bacteria survive antibiotics, the study explored Lyme disease infection in rhesus macaque primates treated with antibiotics and a control group who were also infected but not treated. 

In the study, ticks carrying B. burgdorferi spirochetes fed on ten primates. Four months post infection, half of the primates (five) received the antibiotic doxycycline orally for 28 days at a proportional dose to that used in human treatment...... The results show: Few subjects displayed a rash. Although all subjects were infected, only one of the 10 displayed a rash with central clearing, the classical "bulls-eye" rash. ... Organs may be infected even if antibody tests are negative...... Intact spirochetes were found in three of five treated and four of five untreated subjects based on xenodiagnosis results 12 months after the tick bite.

Immune responses to B. burgdorferi varied greatly posttreatment .... This is significant because it demonstrates that subjects infected with the same strain of B. burgdorferi may have different immune responses to the same antigen. And, because humans, like primates, are genetically diverse, it underscores that testing antibody responses may be inherently unreliable as a singular diagnostic modality for Lyme disease.

Widespread and variable microscopic disease was observed in all infected subjects, despite antibiotic treatment. Compared to uninfected subjects of the same age, infected subjects in this study (treated and untreated) demonstrated inflammation in and around the heart, in skeletal muscles, joints, and the protective sheath that covers the brain, and near peripheral nerves. Rare, but intact B. burgdorferi spirochetes were found in the tissues of both the treated and untreated subjects. In two subjects treated with doxycycline, multiple Lyme bacteria were observed in the brain tissue [Original study.]

I know of a number of people in NY and NJ who have been struggling for years with persistent Lyme disease. So this research with the possibility of treatments that actually work is fantastic. And it gives support to all those people who say they still have Lyme disease after antibiotic treatment, but the medical establishment says they're wrong -  that it's all their mind or due to something else. Yes, they still have Lyme disease from persister cells that avoided the antibiotic treatment! Persister cells are drug-tolerant,dormant variants of Borrelia burgdorferi  (the bacterium that causes Lyme disease). And perhaps pulse-dosing antibiotics may work to get rid of the persister cells. The antibiotic they successfully used in the research is ceftriaxone (a cephalosporin antibiotic) - but only in cultures grown in a lab. Further research is needed. From Science Daily:

Researchers' discovery may explain difficulty in treating Lyme disease

North­eastern Uni­ver­sity researchers have found that the bac­terium that causes Lyme dis­ease forms dor­mant per­sister cells, which are known to evade antibi­otics. This sig­nif­i­cant finding, they said, could help explain why it's so dif­fi­cult to treat the infec­tion in some patients.

In other chronic infec­tions, Lewis' lab has tracked the resis­tance to antibi­otic therapy to the pres­ence of per­sister cells--which are drug-tolerant, dor­mant vari­ants of reg­ular cells. These per­sister cells are exactly what they've iden­ti­fied here in Bor­relia burgdor­feri, the bac­terium that causes Lyme disease.The researchers have also reported two approaches--one of them quite promising--to erad­i­cate Lyme dis­ease, as well as poten­tially other nasty infections.

Lyme dis­ease affects 300,000 people annu­ally in the U.S., according to the Cen­ters for Dis­ease Con­trol and Pre­ven­tion, and is trans­mitted to people via bites from infected black­legged ticks. If caught early, patients treated with antibi­otics usu­ally recover quickly. How­ever, about 10 to 20 per­cent of patients, par­tic­u­larly those diag­nosed later, who have received antibi­otic treat­ment may have per­sis­tent and recur­ring symp­toms including arthritis, muscle pain, fatigue, and neu­ro­log­ical prob­lems. These patients are diag­nosed with Post-treatment Lyme Dis­ease Syndrome.

In addi­tion to iden­ti­fying the pres­ence of these per­sister cells, Lewis' team also pre­sented two methods for wiping out the infection--both of which were suc­cessful in lab tests. One involved an anti-cancer agent called Mit­o­mycin C, which com­pletely erad­i­cated all cul­tures of the bac­terium in one fell swoop. How­ever, Lewis stressed that, given Mit­o­mycin C's tox­i­city, it isn't a rec­om­mended option for treating Lyme dis­ease, though his team's find­ings are useful to helping to better under­stand the disease.

The second approach, which Lewis noted is much more prac­tical, involved pulse-dosing an antibi­otic to elim­i­nate per­sis­ters. The researchers intro­duced the antibi­otic a first time, which killed the growing cells but not the dor­mant per­sis­ters. But once the antibi­otic washed away, the per­sis­ters woke up, and before they had time to restore their pop­u­la­tion the researchers hit them with the antibi­otic again. Four rounds of antibi­otic treat­ments com­pletely erad­i­cated the per­sis­ters in a test tube.

"This is the first time, we think, that pulse-dosing has been pub­lished as a method for erad­i­cating the pop­u­la­tion of a pathogen with antibi­otics that don't kill dor­mant cells," Lewis said. "The trick to doing this is to allow the dor­mant cells to wake up.

This past week I came across two amazing and very different stories, but in both Lyme disease appears. So read with an open mind - because they may or may not work out. But I will say that living in the NY metro area, tick diseases are a big deal, and we all know people who have gotten diseases from ticks. Most get successfully treated with antibiotics, but then there are those people who are suffering years later. The first article is by Dr. Christie Wilcox (a freelance science writer and postdoctoral researcher). Do go read the whole article for her fascinating account of venoms. From Digg:

Poison As Medicine: How A Bee Sting Saved My Life

“I moved to California to die.” Ellie Lobel was 27 when she was bitten by a tick and contracted Lyme disease. And she was not yet 45 when she decided to give up fighting for survival. Caused by corkscrew-shaped bacteria called Borrelia burgdorferi, which enter the body through the bite of a tick, Lyme disease is diagnosed in around 300,000 people every year in the United States. It kills almost none of these people, and is by and large curable – if caught in time. If doctors correctly identify the cause of the illness early on, antibiotics can wipe out the bacteria quickly before they spread through the heart, joints and nervous system.

But back in the spring of 1996, Ellie didn’t know to look for the characteristic bull’s-eye rash when she was bitten – she thought it was just a weird spider bite. Then came three months with flu-like symptoms and horrible pains that moved around the body. Ellie was a fit, active woman with three kids, but her body did not know how to handle this new invader. She was incapacitated. “It was all I could do to get my head up off the pillow,” Ellie remembers.

As time wore on, Ellie went to doctor after doctor, each giving her a different diagnosis. Multiple sclerosis. Lupus. Rheumatoid arthritis. Fibromyalgia. None of them realised she was infected with Borrelia until more than a year after she contracted the disease – and by then, it was far too late. Lyme bacteria are exceptionally good at adapting, with some evidence that they may be capable of dodging both the immune system and the arsenal of antibiotics currently available. Borrelia are able to live all over the body, including the brain, leading to neurological symptoms. And even with antibiotic treatment, 10–20 per cent of patients don’t get better right away. There are testimonies of symptoms persisting – sometimes even resurfacing decades after the initial infection – though the exact cause of such post-treatment Lyme disease syndrome is a topic of debate among Lyme scientists.

I just kept doing this treatment and that treatment,” says Ellie. Her condition was constantly worsening....So she packed up everything and moved to California to die. And she almost did. Less than a week after moving, Ellie was attacked by a swarm of Africanised bees....Bees – and some other species in the order Hymenoptera, such as ants and wasps – are armed with a potent sting that many of us are all too aware of. This is their venom, and it’s a mixture of many compounds. Perhaps the most important is a tiny 26-amino-acid peptide called melittin, which constitutes more than half of the venom of honey bees and is found in a number of other bees and wasps. 

“I just went limp. I put my hands up and covered my face because I didn’t want them stinging me in the eyes… The next thing I know, the bees are gone.” When the bees finally dissipated, her caregiver tried to take her to the hospital, but Ellie refused to go... But Ellie didn’t die. Not that day, and not three to four months later...She believes the bees, and their venom, saved her life.

The idea that the same venom toxins that cause harm may also be used to heal is not new. Bee venom has been used as a treatment in East Asia since at least the second century BCE...Despite the wealth of history, the practical application of venoms in modern therapeutics has been minimal....Over the course of the 20th century, suggested venom treatments for a range of diseases have appeared in scientific and medical literature. Venoms have been shown to fight cancer, kill bacteria, and even serve as potent painkillers – though many have only gone as far as animal tests

The more we learn about the venoms that cause such awful damage, the more we realise, medically speaking, how useful they can be. Like the melittin in bee venomMelittin does not only cause pain. In the right doses, it punches holes in cells’ protective membranes, causing the cells to explode. At low doses, melittin associates with the membranes, activating lipid-cutting enzymes that mimic the inflammation caused by heat. But at higher concentrations, and under the right conditions, melittin molecules group together into rings creating large pores in membranes, weakening a cell’s protective barrier and causing the entire cell to swell and pop like a balloon.Because of this, melittin is a potent antimicrobial, fighting off a variety of bacteria and fungi with ease. 

After the attack, Ellie watched the clock, waiting for anaphylaxis to set in, but it didn’t. Instead, three hours later, her body was racked with pains. A scientist by education before Lyme took its toll, Ellie thinks that these weren’t a part of an allergic response, but instead indicated a Jarisch–Herxheimer reaction – her body was being flooded with toxins from dying bacteria. The same kind of thing can happen when a person is cured from a bad case of syphilis. A theory is that certain bacterial species go down swinging, releasing nasty compounds that cause fever, rash and other symptoms. For three days, she was in pain. Then, she wasn’t.“I had been living in this… I call it a brown-out because it’s like you’re walking around in a half-coma all the time with the inflammation of your brain from the Lyme. My brain just came right out of that fog. I thought: I can actually think clearly for the first time in years.”

With a now-clear head, Ellie started wondering what had happened. So she did what anyone else would do: Google it. Disappointingly, her searches turned up very little. But she did find one small 1997 study by scientists at the Rocky Mountain Laboratories in Montana, who’d found that melittin killed Borrelia. Exposing cell cultures to purified melittin, they reported that the compound completely inhibited Borrelia growth. When they looked more closely, they saw that shortly after melittin was added, the bacteria were effectively paralysed, unable to move as their outer membranes were under attack. Soon after, those membranes began to fall apart, killing the bacteria.

Convinced by her experience and the limited research she found, Ellie decided to try apitherapy, the therapeutic use of materials derived from bees...She started on a regimen of ten stings a day, three days a week: Monday, Wednesday, Friday. Three years and several thousand stings later, Ellie seems to have recovered miraculously. Slowly, she has reduced the number of stings and their frequency – just three stings in the past eight months, she tells me (and one of those she tried in response to swelling from a broken bone, rather than Lyme-related symptoms). 

Since the 1997 study, no one had looked further into bee venom as a potential cure for Lyme disease, until Ellie. Ellie now runs a business selling bee-derived beauty products called BeeVinity, inspired after, she says, noticing how good her skin looked as she underwent apitherapy.....In addition, she sends some of the venom she purchases – which, due to the cost of the no-harm extraction method she uses, she says is “more expensive than gold” – to Eva Sapi, Associate Professor of Biology and Environmental Science at the University of New Haven, who studies Lyme disease.

Sapi’s research into the venom’s effects on Lyme bacteria is ongoing and as yet unpublished, though she told me the results from preliminary work done by one of her students look “very promising”. Borrelia bacteria can shift between different forms in the body, which is part of what makes them so hard to kill. Sapi has found that other antibiotics don’t actually kill the bacteria but just push them into another form that is more dormant. As soon as you stop the antibiotics, the Borrelia bounce back. Her lab is testing different bee venoms on all forms of the bacteria, and so far, the melittin venom seems effective...And they still don’t really know why the venom works for Ellie, not least because the exact cause of post-treatment Lyme disease symptoms remains unknown. “Is it effective for her because it’s killing Borrelia, or is it effective because it stimulates the immune system?” asks Sapi. It’s still a mystery.